Trial reportCancer chemotherapy and pharmacology2013
Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers.
Trial report in Cancer chemotherapy and pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Integration of healthy volunteers in early phase clinical trials with immuno-oncological compounds.Frontiers in oncology · 2022Pooled it
- Evaluation of drug-drug interactions between midostaurin and strong CYP3A4 inhibitors in patients with FLT-3-mutated acute myeloid leukemia (AML).Cancer chemotherapy and pharmacology · 2022Trial
- Interaction potential of the dual orexin receptor antagonist ACT-541468 with CYP3A4 and food: results from two interaction studies.European journal of clinical pharmacology · 2019Trial
- Comparison of two endogenous biomarkers of CYP3A4 activity in a drug-drug interaction study between midostaurin and rifampicin.European journal of clinical pharmacology · 2014Trial
- The type I FLT3 inhibitor XL999 overrides secondary FLT3-ITD mutations that arise under gilteritinib and quizartinib treatment in acute myeloid leukemia.Molecular biomedicine · 2026Article
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Comparative Analysis of Isavuconazole DDIs With Other Azole Antifungal Drugs and PBPK Model-Informed Dosing Recommendations for Anticancer Drugs.CPT: pharmacometrics & systems pharmacology · 2025Article
- Challenges in Extrapolating Healthy Volunteer Pharmacokinetics to Oncology Populations: Advocating for a Holistic Perspective.Clinical and translational science · 2025Review
- Optimization of In Vitro CYP3A4 TDI Assay Conditions and Use of Derived Parameters for Clinical DDI Risk Assessment Using Static and Dynamic Models.The AAPS journal · 2025Article
- The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers.Pharmacotherapy · 2025Article
- Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer.Molecular biomedicine · 2025Review
- Effect of midostaurin on the pharmacokinetics of P-gp, BCRP, and CYP2D6 substrates: assessing potential drug-drug interactions in healthy participants : Brief title: Drug-drug interaction of midostaurin.Cancer chemotherapy and pharmacology · 2024Article
- Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals.European journal of drug metabolism and pharmacokinetics · 2024Article
- Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.Cancer chemotherapy and pharmacology · 2024Article
- Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches.Frontiers in oncology · 2024Review
- Recommendations on the use of azole antifungals in hematology-oncology patients.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023Review
- "FLipping" the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors.Cancers · 2022Review
- The Protein Kinase Inhibitor Midostaurin Improves Functional Neurological Recovery and Attenuates Inflammatory Changes Following Traumatic Cervical Spinal Cord Injury.Biomolecules · 2021Article
- How I Treat Febrile Neutropenia.Mediterranean journal of hematology and infectious diseases · 2021Review
- Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia.Journal of clinical pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMidostaurin (PKC412), a multitargeted tyrosine kinase inhibitor that targets FMS-related tyrosine kinase 3 and KIT, is in clinical trials for the treatment for acute myeloid leukemia and advanced systemic mastocytosis. In vitro studies showed that midostaurin is predominantly metabolized by cytochrome P450 3A4 (CYP3A4) and that midostaurin inhibits and/or induces the same enzyme. Here, we address the clinical relevance of CYP3A4-related drug-drug interactions with midostaurin as either a "victim" or "perpetrator."
methodsThree phase I studies in healthy volunteers evaluated the effects of a CYP3A4 inhibitor (ketoconazole 400 mg daily for 10 days) or CYP3A4 inducer (rifampicin 600 mg daily for 14 days) on concentrations of midostaurin and its metabolites following a single 50-mg dose of midostaurin and the effects of midostaurin as a single dose (100 mg) and multiple doses (50 mg twice daily) on midazolam (a sensitive CYP3A4 probe) concentration. The plasma concentrations of midostaurin and its 2 active metabolites, CGP62221 and CGP52421, were determined using a sensitive liquid chromatography/tandem mass spectrometry method.
resultsInhibition of CYP3A4 by ketoconazole increased midostaurin exposure more than tenfold, and induction of CYP3A4 by rifampicin decreased midostaurin exposure by more than tenfold. Midostaurin did not appreciably affect the concentrations of midazolam or its metabolite, 1'-hydroxymidazolam, at single or multiple doses.
conclusionThe pharmacokinetics of midostaurin and its metabolites was affected substantially by ketoconazole and rifampicin, suggesting that midostaurin is a sensitive CYP3A4 substrate. Midostaurin did not appear to inhibit or induce CYP3A4 in vivo.
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